The spleen focus-forming virus (SFFV) and Friend mink cell focus-inducing virus (Fr-MCF) both induce eythroleukemia in susceptible strains of mice. Studies are being carried out to determine which areas of the viral genomes are important in the development of disease and to determine how their products specifically interfere with erythroid cell growth and differentiation. The envelope genes and LTR regions of several strains of SFFV have been sequenced and compared with those of other murine leukemia viruses, and specific, highly conserved changes have been found. Attempts are being made to determine which changes are crucial for pathogenicity and target cell specificity. Additional information about the viral envelope genes and the role of their products in pathogenicity have come from further characterization of the proteins and analysis of their expression in various tissues. In order to determine the mechanisms by which SFFV and Fr-MCF virus alter erythropoiesis, hematopoietic cells from mice infected with these viruses have been analyzed for their ability to proliferate in the presence or absence of the hormone erythropoietin and attempts have been made to determine if their envelope gene products are related to this hormone or its receptor. Finally, attempts to further define the gene in DBA/2 mice responsible for resistance of these mice to F-MuLV-induced erythroleukemia have suggested that it is a single gene on chromosone 5 but is not the RMCFr gene. Additional studies are being carried out to further define this resistance as well as the resistance that exists in adult mice of susceptible strains.